2010
Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis
Korman TP, Crawford JM, Labonte JW, Newman AG, Wong J, Townsend CA, Tsai SC. Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 6246-6251. PMID: 20332208, PMCID: PMC2851968, DOI: 10.1073/pnas.0913531107.Peer-Reviewed Original ResearchConceptsPolyketide synthasesCrystal structureC bond formationPolyketide natural productsProduct release mechanismRing closure reactionAlpha/beta hydrolase foldSynthetic versatilitySynthetic potentialSubstrate-binding chamberIterative polyketide synthasesC cyclizationFatty acid synthasesBond formationClaisen cyclizationFirst mechanistic insightsProtein conformational changesNatural productsClosure reactionSubstrate positioningSide chainsBiosynthesis of aflatoxinSubstrate side chainDiverse architecturesPolyketide synthase AAbsence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures
Ehrlich KC, Chang P, Scharfenstein LL, Cary JW, Crawford JM, Townsend CA. Absence of the aflatoxin biosynthesis gene, norA, allows accumulation of deoxyaflatoxin B1 in Aspergillus flavus cultures. FEMS Microbiology Letters 2010, 305: 65-70. PMID: 20158523, PMCID: PMC2891446, DOI: 10.1111/j.1574-6968.2010.01914.x.Peer-Reviewed Original ResearchConceptsBiosynthetic gene clusterAflatoxin biosynthesis genesCytochrome P450 monooxygenaseAflatoxin biosynthetic gene clusterWild-type A. flavusBiosynthesis genesGene clusterP450 monooxygenaseAflatoxin biosynthesisCarcinogenic aflatoxinsAccumulation of aflatoxinBiosynthesisA. flavusMinor toxinsO-methylsterigmatocystinAspergillus speciesFinal stepAspergillus flavusNew metabolitesQuantities of aflatoxinElevated quantitiesMutantsAccumulationFlavusGenes
2008
Starter unit specificity directs genome mining of polyketide synthase pathways in fungi
Crawford JM, Vagstad AL, Ehrlich KC, Townsend CA. Starter unit specificity directs genome mining of polyketide synthase pathways in fungi. Bioorganic Chemistry 2008, 36: 16-22. PMID: 18215412, PMCID: PMC3200548, DOI: 10.1016/j.bioorg.2007.11.002.Peer-Reviewed Original ResearchConceptsHybrid metabolitesPathogenic fungus Coccidioides immitisPolyketide synthase pathwayHuman fungal pathogenSAT domainAflatoxin clusterGenome miningSynthase subunitsPolyketide synthasePKS clustersACP domainStarter unitProtein databasePolyketide synthesisFungal pathogensFunctional similarityHexanoyl-CoA.Fatty acid productsEscherichia coliSynthase pathwayFungiFungus Coccidioides immitisAspergillus speciesPathwayDomain
2006
Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase
Crawford JM, Dancy BC, Hill EA, Udwary DW, Townsend CA. Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 16728-16733. PMID: 17071746, PMCID: PMC1636523, DOI: 10.1073/pnas.0604112103.Peer-Reviewed Original Research